DE69707363T2

DE69707363T2 - 1,2,3-benzothiadiazole derivatives and their use as microbicides

Info

Publication number: DE69707363T2
Application number: DE69707363T
Authority: DE
Inventors: Yasuo Araki; Koichi Ishikawa; Taro Kinbara; Yoshio Kurahashi; Koichi Moriya; Asami Motonaga; Haruko Sawada
Original assignee: Nihon Bayer Agrochem KK
Current assignee: Bayer CropScience KK
Priority date: 1996-07-05
Filing date: 1997-06-23
Publication date: 2002-05-02
Anticipated expiration: 2017-06-24
Also published as: US5869508A; ES2166026T3; KR980009261A; EP0816363A1; JPH1017566A; EP0816363B1; CN1172111A; DE69707363D1; US6153763A; CA2209520A1; CN1084746C

Description

The present invention relates to novel 1,2,3-benzothiadiazole derivatives, processes for their preparation and their use as microbicides. Furthermore, the invention relates to novel intermediate compounds and processes for their preparation.

It is already known that certain 1,2,3-benzothiadiazole derivatives have fungicidal properties (see JP-OS 1-90 176, 3-169 872, 5-97 829, 5-194 450 and 8-53 464 and GB-A 1 176 799). However, the effectiveness of these substances is not always good enough, especially when they are used in small doses.

Furthermore, some processes for the synthesis of 1,2,3-benzothiadiazole derivatives have already been described (see J. Chem.Soc. 1967, 321-323, 1970, 2514-2518, 1970, 2250-2252 and 3971, 3994-3999). However, the availability of further processes for the preparation of such compounds is still desirable.

New 1,2,3-benzothiadiazole derivatives of the formula have now been discovered:

where Het is:

and what

R¹ hydrogen, C1-4 alkyl, C1-4 haloalkyl, phenyl-C1-4 alkyl, cyano-C1-4 alkyl, C1-2 alkoxy-C1-4 alkyl, C 1-2 alkylthio-C1-4 alkyl, C1-2 alkoxycarbonyl-C1-4 ₄-alkyl, C₂₋₄-alkenyl, phenyl, halogen-substituted phenyl or C₁₋₄-alkyl-substituted phenyl and

R² and R³ are independently hydrogen or C₁₋₄-alkyl, as well as acid addition salts and metal salt complexes thereof.

It has further been found that 1,2,3-benzothiadiazole derivatives of formula (I) and acid addition salts and metal salt complexes thereof can be prepared by

a) 1,2,3-benzothiadiazolylcarbonyl halides of the formula:

where Hal is chlorine or bromine,

with heterocycles of the formula:

Het¹-H (III),

where Het¹ represents:

in which

R&sup4; C1-4 alkyl, C1-4 haloalkyl, phenyl-C1-4 alkyl, cyano-C1-4 alkyl, C1-2 alkoxy-C1-4 alkyl, submin 2 -alkylthio-C 1-4 alkyl, C 1-2 alkoxycarbonyl-C 1-4 alkyl, C 2-4 alkyl. 4 -alkenyl, phenyl, halogen-substituted phenyl or C 1-4 alkyl-substituted phenyl,

or in which

Het¹ represents:

wherein

R² and R³ have the meanings given above,

in the presence of an inert diluent and, if appropriate, in the presence of a binding agent for acids,

or by

b) Phenyl derivatives of the formula:

wherein

Het¹ has the meanings given above and

R⁵ is hydrogen, methyl, isopropyl, benzyl or acetyl,

with nitrous acid or a salt thereof in the presence of an inert diluent under acidic conditions,

or by

c) 1,2,3-benzothiadiazole derivatives of the formula:

wherein

Het² is:

with an acid and, if appropriate, in the presence of an inert diluent,

or by

d) 1,2,3-benzothiadiazole derivatives of the formula:

wherein

Het³ is:

with halogen compounds of the formula:

R6-Hal¹ (V),

in which

R&sup6; C1-4 alkyl, C1-4 haloalkyl, phenyl-C1-4 alkyl, cyano-C1-4 alkyl, C1-2 alkoxy-C1-4 alkyl, submin2 -alkylthio-C1-4 alkyl, C1-2 alkoxycarbonyl-C1-4 alkyl or C2-4 alkenyl and

Hal¹ are chlorine, bromine or iodine,

and, if appropriate, an acid or a metal salt is added to the 1,2,3-benzothiadiazole derivatives of the formula (I) thus obtained.

Finally, it has been found that the 1,2,3-benzothiadiazole derivatives of formula (I) and acid addition salts and metal salt complexes thereof are extremely active as microbicides which can be applied in agriculture and horticulture. They can be used either to directly control undesirable microorganisms such as phytopathogenic fungi and bacteria or to induce resistance to phytopathogenic fungi and bacteria in the plant bodies themselves.

Surprisingly, the compounds according to the invention show and provide a much better fungicidal activity than the already known compounds which are structurally most similar and have the same type of action.

In the given context, "alkyl" represents straight-chain or branched groups. The term "alkyl" includes, for example, methyl, ethyl, propyl, isopropyl and n-(iso-, sec- and t-)butyl. Said "alkyl" may be substituted and the corresponding substituents include halogen, such as fluorine, chlorine or bromine, cyano, alkoxy, such as meth-, eth- or propoxy, alkylthio, such as methylthio- or ethylthio, alkoxycarbonyl, such as meth- or ethoxycarbonyl, and phenyl.

The term "alkenyl", in the given context, also represents straight-chain or branched groups. It includes, for example, vinyl, allyl, isopropenyl and 1-methyl-2-propenyl.

Formula (I) provides a general definition of the 1,2,3-benzothiadiazole derivatives according to the invention. Preferred compounds of formula (I) are those in which Het is:

wherein

R¹ hydrogen, methyl, ethyl, propyl, isopropyl, butyl, cyanomethyl, 2-cyanoethyl, 1-cyanoethyl, 3-cyanopropyl, methoxymethyl, ethoxymethyl, methylthiomethyl, methoxycarbonylethyl, ethoxycarbonylmethyl, ethoxycarbonylethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, benzyl, phenyl, chlorophenyl, methylphenyl, vinyl, allyl or -en-1-yl and

R² and R³, independently of each other, are hydrogen, methyl, ethyl, propyl or isopropyl.

Addition products of acids and those 1,2,3-benzothidiazole derivatives of the formula (I) in which Het has the meanings already mentioned as preferred for this radical also represent preferred compounds according to the invention.

The acids which can be added preferably include hydrohalic acids, such as hydrochloric and hydrobromic acid, in particular hydrochloric acid and, furthermore, phosphoric, nitric, sulphuric, mono- and bifunctional carboxylic acids and hydroxycarboxylic acids, such as acetic, maleic, succinic, fumaric, tartaric, citric, salicylic, sorbic and lactic acid, and sulphonic acids such as p-toluene, 1,5-naphthalenedisulphonic acid or camphorsulphonic acid, as well as saccharin and thiosaccharin.

Addition products of the salts of metals of main groups II to IV and subgroups I and II and IV to VIII of the Periodic Table of the Elements and those 1,2,3-benzothiadiazole derivatives of the formula (I) in which Het has the meanings already mentioned as preferred for this radical are also preferred compounds according to the invention.

Salts of copper, zinc, manganese, magnesium, tin, iron and nickel are particularly preferred here. Possible anions of these salts are those derived from those acids which lead to physiologically acceptable addition products. Particularly preferred acids of this type are, in the given context, the hydrohalic acids, such as hydrochloric and hydrobromic acid, and also phosphoric, nitric and sulphuric acid.

Specific examples of 1,2,3-benzothiadiazole derivatives of formula (I) are listed in Table 1 below. Table 1 Table 1 (continued) Table 1 (continued) Table 1 (continued) Table 1 (continued)

When using 7-chlorocarbonyl-1,2,3-benzothiadiazole and 1-methylimidazole as starting materials, the course of process (a) according to the invention can be represented by the following formula scheme:

When using 2-(3'-amino-2'-benzylthiobenzoyl)-1-methylimidazole and nitrous acid as starting materials, the course of process (b) according to the invention can be represented by the following formula scheme:

Using 5-(1',2',3'-benzothiadiazol-7'-yl)carbonyl-1-methoxymethyl-1,2,4-triazole and concentrated hydrochloric acid as starting materials, the course of process (c) according to the invention can be represented by the following formula scheme:

When using 3-(1',2',3'-benzothiadiazol-7'-yl)carbonyl-1,2,4-triazole and methyl iodide as starting materials, the course of process (d) according to the invention can be represented by the following formula scheme:

Formula (II) provides a general definition of the 1,2,3-benzothiadiazolylcarbonyl halides required as starting materials for carrying out process (a) according to the invention. In this formula, Hal denotes chlorine or bromine.

Specific examples of the compound of formula (II) are 7-chloro- and 7-bromocarbonyl-1,2,3-benzothiadiazole.

The 1,2,3-benzothiadiazolylcarbonyl halides of the formula (II) are known (see JP-OS 1-90 176).

Formula (III) provides a general definition of the heterocycles required as reaction components for carrying out the process (a) according to the invention.

In this formula, Het¹ is preferably:

wherein

R&sup4; preferably methyl, ethyl, propyl, isopropyl, butyl, cyanomethyl, 2-cyanoethyl, 1-cyanoethyl, 3-cyanopropyl, methoximethyl, ethoxymethyl, methylthiomethyl, methoxycarbonylethyl, ethoxycarbonylmethyl, ethoxycarbonylethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, benzyl, phenyl, chlorophenyl, methylphenyl, vinyl, alkyl or but-3-ene 1-yl is,

or

Het¹ is:

wherein

R² and R³, independently of each other, are hydrogen, methyl, ethyl, propyl, isopropyl or t-butyl.

The following compounds can be mentioned as examples of heterocycles of formula (III):

1-methylimidazole, 1-ethylimidazole, 1-n-propylimidazole, 1-isopropylimidazole, 1-vinylimidazole, 1-cyanomethylimidazole, 1-(2-cyanoethyl)imidazole, 1-Difluoromethylimidazole, 1-(methoxymethyl)imidazole, 1-(methoxycarbonylmethyl)imidazole, 1-phenylimidazole, thiazole, 4-methylthiazole, 5-methylthiazole, 4,5-dimethylthiazole, benzothiazole, 4,5,6,7-tetrahydrobenzothiazole, 1-methyl-1,2,4-triazole, 1-ethyl-1 ,2,4-triazole, 1-n-propyl-1,2,4-triazole, 1-isopropyl-1,2,4-triazole, 4-methyl-1,2,4-triazole, 1-difluoromethyl-1,2,4-triazole, 1-cyanomethyl-1,2,4-triazole, 1-(2-cyanoethyl)-1,2,4-triazole, 1-Methoxymethyl-1,2,4-triazole, 1-methylthiomethyl-1,2,4-triazole, 1-vinyl-1,2,4-triazole, 1-phenyl-1,2,4-triazole and 1-benzyl-1,2,4-triazole.

The heterocycles of formula (III) are known.

Formula (IV) provides a general definition of the phenyl derivatives required as starting materials for carrying out process (b) according to the invention. In this formula, Het¹ preferably has those meanings which have already been mentioned as preferred for this substituent. R⁵ is preferably benzyl.

The phenyl derivatives of formula (IV) are new. They can be prepared by

e) Nitrophenyl derivatives of the formula:

wherein

Het¹ and R&sup5; have the above meanings,

with reducing agents in the presence of an inert diluent and, optionally, in the presence of a catalyst.

The nitrophenyl derivatives of formula (VI) are also new. They can be prepared by

f) Chloronitrophenyl derivatives of the formula:

wherein

Het¹ has the above meanings,

with sulphur compounds of the formula:

HS-R5 (VIII),

in which R&sup5; has the above meanings,

in the presence of an inert diluent and, optionally, in the presence of a binder for acids.

The chloronitriophenyl derivatives of formula (VII) are also new. They can be prepared by

g) 2-chloro-3-nitrobenzoyl chloride of the formula:

with a heterocycle of the formula:

Het¹-H (III),

where Het¹ has the above meanings,

in the presence of an inert diluent and, if appropriate, in the presence of a binder for acids.

2-Chloro-3-nitrobenzoyl chloride of formula (IX) is a known compound.

The heterocycles of the formula (III) are also known. Specific examples include imidazole, benzimidazole, 1,2,4-triazole, thiazole, 4-methylthiazole, 5-methylthiazole, 4,5-dimethylthiazole, benzothiazole, 4,5,6,7-tetrahydrobenzothiazole, and the compounds specifically mentioned as examples of heterocycles of the above formula (III).

Process (g) is carried out under reaction conditions corresponding to those of process (a) (see below).

Processes (e) and (f) are carried out under reaction conditions corresponding to those known from Japanese Patent Application Laid-Open No. 1-90,176.

Formula (VIII) provides a general definition of the sulphur compounds required as reaction components for carrying out process (f). In this formula, R5 preferably has those meanings which have already been mentioned as preferred for this substituent.

Specific examples of sulfur compounds of formula (VIII) include benzyl, methyl and isopropyl mercaptan.

The sulfur compounds of formula (VIII) are known.

Formula (Ia) provides a general definition of the 1,2,3-benzothiadiazole derivatives which can be used as starting materials for carrying out the process (c) according to the invention. In this formula, Het² preferably has the meanings already mentioned above for this radical.

Specific examples of the compounds of formula (Ia) include

2-(1',2',3'-benzothiadiazol-7'-yl)carbonyl-1-methoxymethylimidazole, 2-(1',2',3'-benzothiadiazol-7'-yl)carbonyl-2-methoxymethylbenzimidazole and 5-(1',2',3'-benzothiadiazol-7'-yl)carbonyl-1-methoxymethyl-1,2,4-triazole.

The 1,2,3-benzothiadiazole derivatives of formula (Ia) are compounds according to the invention which can be prepared according to the above-mentioned process (a).

Formula (Ib) provides a general definition of the 1,2,3-benzothiadiazole derivatives required as starting materials for carrying out the process (d) according to the invention. In this formula, Het³ preferably has the meanings already mentioned above for this radical.

Specific examples of the compounds (Ib) include 2-(1',2',3'-benzothiadiazol-7'-yl)carbonylimidazole, 2-(1',2',3'-benzothiadiazol-7'-yl)carbonylbenzimidazole and 5-(1',2',3'-benzothiadiazol-7'-yl)carbonyl-1,2,4-triazole.

The 1,2,3-benzothiadiazole derivatives of formula (Ib) are compounds according to the invention which can be prepared according to the above-mentioned processes (b) and (c).

Formula (V) provides a general definition of the halogen compounds required as reaction components for carrying out the process (d) according to the invention. In this formula,

R&sup6; preferably methyl, ethyl, propyl, isopropyl, butyl, cyanomethyl, 2-cyanoethyl, 1-cyanoethyl, 3-cyanopropyl, methoximethyl, ethoxymethyl, methylthiomethyl, methoxycarbonylethyl, ethoxycarbonylmethyl, ethoxycarbonylethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, vinyl, allyl or but-3-en-1-yl and

Hal¹ preferably chlorine, bromine or iodine.

Specific examples of halogen compounds of formula (V) include methyl iodide, ethyl iodide, propyl iodide, isopropyl iodide, cyanomethyl iodide, methoxymethyl chloride, methylthiomethyl chloride, chlorodifluoromethane, cyanoethyl bromide, allyl bromide, methyl chloroacetate, ethyl chloroacetate, ethyl 3-chloropropionate, ethyl 2-chloropropionate, methyl 3-chloropropionate and methyl 2-chloropropionate.

The halogen compounds of formula (V) are known.

All inert organic solvents which are customary for such reactions can be used as diluents for carrying out the process (a) according to the invention. Suitable solvents are preferably aliphatic, alicyclic or aromatic hydrocarbons (which may optionally be chlorinated), such as pentane, hexane, cyclohexane, petroleum ether, ligroin, benzene, toluene, xylene, dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, chlorobenzene or dichlorobenzene, ethers such as diethyl ether, methyl ethyl ether, diisopropyl ether, dibutyl ether, dioxane, dimethoxyethane (DME), tetrahydrofuran (THF) or diethylene glycol dimethyl ether (DGM), nitriles such as acetonitrile, propionitrile or acrylonitrile, esters such as ethyl or amyl acetate, acid amides such as dimethylformamide (DMF), dimethylacetamide (DMA), N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone or hexamethylphosphoric triamide (HMPA) and sulfones and sulfoxides such as Dimethyl sulfoxide (DMSO) or sulfolane as well as bases such as pyridine.

The process (a) can be carried out in the presence of a binder for acids. Suitable binders for the acids are organic bases, e.g. tertiary amines, dialkylaminoanilines and pyridines, such as triethylamine, 1,1,4,4-tetramethylethylenediamine (TMEDA), N,N-dimethylaniline, N,N-diethylaniline, pyridine, 4-dimethylaminopyridine (OMAP), 1,4-diazabicyclo-(2.2.2)octane (DABCO) or 1,8-diazabicyclo[5.4.0]undec-6-ene (DBU).

To carry out process (a) according to the invention, the reaction temperatures can be varied within a fairly wide range. The reaction is generally carried out at a temperature of from -75 to about +100 and preferably from about 0 to about 100°C.

The process (a) according to the invention is generally carried out under atmospheric pressure, but optionally also under elevated or reduced pressure.

To carry out process (a) according to the invention, in general 1 mole of 1,2,3-benzothiadiazolylcarbonyl halide of the formula (II) is reacted with 0.1 to 10 moles of a heterocycle of the formula (III) in the presence of a diluent, such as dichloromethane, and optionally in the presence of a binding agent for acids, such as pyridine. Work-up is carried out using conventional methods.

The process (b) according to the invention can be carried out in the presence of all diluents which are customary for such reactions. Suitable diluents are preferably water, hydrochloric, acetic and sulphuric acid, aliphatic, alicyclic or aromatic hydrocarbons (which may optionally be chlorinated), such as pentane, hexane, cyclohexane, petroleum ether, ligroin, benzene, toluene, xylene, dichloromethane, chloroform, Carbon tetrachloride, 1,2-dichloroethane, chloro- or dichlorobenzene, ethers such as diethyl ether, methyl ethyl ether, diisopropyl ether, dibutyl ether, dioxane, dimethoxyethane (DME), tetrahydrofuran (THF) or diethylene glycol dimethyl ether (DGM), nitriles such as acetonitrile, propionitrile or acrylonitrile, esters such as ethyl or amyl acetate, acid amides such as dimethylformamide (DMF), dimethylacetamide (DMA), N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone or hexamethylphosphoric triamide (HMPA) as well as sulfones and sulfoxides such as dimethyl sulfoxide (DMSO) or sulfolane.

To carry out process (b) according to the invention, the reaction temperatures can be varied within a fairly wide range. The reaction is generally carried out at a temperature of from -20 to about +100 and preferably from about 0 to about 80°C.

The process (b) according to the invention is preferably carried out under atmospheric pressure, but can optionally also be carried out under elevated or reduced pressure.

To carry out process (b) according to the invention, in general 1 mole of phenyl derivative of formula (IV) is reacted with 1 to 10 moles of nitrous acid or a salt thereof in the presence of a diluent, such as water, under acidic conditions. Work-up is carried out by conventional methods.

The process (c) according to the invention can also be carried out in the presence of all diluents which are customary for such reactions. Suitable diluents are preferably water, aliphatic, alicyclic or aromatic hydrocarbons (which may optionally be chlorinated), such as pentane, hexane, cyclohexane, petroleum ether, ligroin, benzene, toluene, xylene, dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, chloro- or dichlorobenzene, ethers such as diethyl ether, methyl ethyl ether, diisopropyl ether, dibutyl ether, dioxane, dimethoxyethane (DME), tetrahydrofuran (THF) or diethylene glycol dimethyl ether (DGM), ketones such as acetone, methyl ethyl ketone (MEK), methyl isopropyl ketone or methyl isobutyl ketone (MIBK), nitriles such as acetonitrile, propionitrile or acrylonitrile, alcohols such as methanol, ethanol, isopropanol, butanol or ethylene glycol, esters such as ethyl or amyl acetate, acid amides such as dimethylformamide (DMF), Dimethylacetamide (DMA), N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone and hexamethylphosphoric triamide (HMPA) and sulfones and sulfoxides such as dimethyl sulfoxide (DMSO) or sulfolane.

The process (c) according to the invention is carried out in the presence of an acidic compound. Suitable acidic compounds are preferably mineral acids such as hydrochloric, sulphuric, phosphoric and hydrobromic acid or sodium hydrogen sulfide, organic acids such as formic, acetic, trifluoroacetic, propionic, methanesulfonic, benzenesulfonic or p-toluenesulfonic acid and organic amine hydrochlorides such as pyridine and triethylamine hydrochloride.

To carry out process (c) according to the invention, the reaction temperatures can be varied within a fairly wide range. The reaction is generally carried out at a temperature of from about -20 to about +150 and preferably from about 0 to about 120°C.

The process (c) according to the invention is generally carried out under atmospheric pressure, but can, if necessary, also be carried out under elevated pressure.

To carry out process (c) according to the invention, in general 1 mole of 1,2,3-benzothiadiazole derivative of formula (Ia) is reacted with an equimolar amount or an excess of an acidic compound, such as concentrated hydrochloric acid, in the presence of a diluent, such as water. Work-up is carried out by conventional methods.

To carry out the process (d) according to the invention, all inert organic solvents which are customary for such reactions can be used as diluents. Suitable diluents are preferably aliphatic, alicyclic or aromatic hydrocarbons (which may optionally be chlorinated), such as pentane, hexane, cyclohexane, petroleum ether, ligroin, benzene, toluene, xylene, dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, chloro- or dichlorobenzene, ethers such as diethyl ether, methyl ethyl ether, diisopropyl ether, dibutyl ether, dioxane, dimethoxyethane (DME), tetrahydrofuran (THF) or diethylene glycol dimethyl ether (DGM), ketones such as acetone, methyl ethyl ketone (MEK), methyl isopropyl ketone or methyl isobutyl ketone (MIBK), nitriles such as acetonitrile, propionitrile or acrylonitrile, alcohols such as methanol, ethanol, isopropanol, butanol or ethylene glycol, esters such as ethyl or amyl acetate, acid amides such as dimethylformamide (DMF), Dimethylacetamide (DMA), N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone and hexamethylphosphoric triamide (HMPA) as well as sulfones and sulfoxides such as dimethyl sulfoxide (DMSO) or sulfolane.

The process (d) according to the invention can also be carried out in the presence of a binding agent for acids. Suitable acid binders are preferably organic binders, e.g. hydroxides, carbonates and bicarbonates of alkali or alkaline earth metals, such as sodium hydrogen carbonate, potassium hydrogen carbonate, sodium carbonate, potassium carbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide or calcium hydroxide, alkali metal amides, e.g. lithium, Sodium or potassium amide, organic bases, e.g. alcoholates, tertiary amines, dialkylaminoanilines and pyridines, such as triethylamine, 1,1,4,4-tetramethylethylenediamine (TMEDA), N,N-dimethylaniline, N,N-diethylaniline, pyridine, 4-dimethylaminopyridine (DMAP), 1,4-diazabicyclo[2.2.2]octane (DABCO) or 1,8-diazabicyclo[5.4.0]undec-6-ene (DBU), and organic lithium compounds, e.g. B. Methyllithium, n-butyllithium, sec-butyllithium, t-butyllithium, phenyllithium, dimethylcopperlithium, lithium diisopropylamide, lithium cyclohexylisopropylamide, lithium dicyclohexylamide, n-butyllithium x DABCO, n-butyllithium x DBU and n-butyllithium x TMEDA.

To carry out process (d) according to the invention, the reaction temperatures can be varied within a fairly wide range. The reaction is generally carried out at a temperature of about -70 to +150 and preferably of about 0 to 120°C.

The process (d) according to the invention is generally carried out under atmospheric pressure, but can also, if appropriate, be carried out under elevated pressure.

To carry out process (d) according to the invention, in general 1 mole of 1,2,3-benzothiadiazole derivative of formula (Ib) is reacted with 1 to 1.5 moles of a halogen compound of formula (V) in the presence of a diluent such as acetonitrile and optionally in the presence of a binding agent for acids such as sodium carbonate. Work-up is carried out using conventional methods.

The 1,2,3-benzothiadiazole derivatives of formula (I) can be converted into acid addition salts and metal salt complexes.

The acids which have already been mentioned as preferred acids in connection with the description of the acid addition salts according to the invention can preferably be used to prepare acid addition salts of the compounds (I).

The acid addition salts of the compounds of formula (I) can be obtained in a simple manner by conventional salt formation processes, for example by dissolving a compound of formula (I) in an inert solvent and adding the acid, e.g. hydrochloric acid, and they can then be isolated in a known manner, e.g. by filtration, and optionally purified by washing with an inert organic solvent.

Those salts of metals which have already been mentioned as preferred metal salts in connection with the description of the metal salt complexes according to the invention can preferably be used to prepare metal salt complexes of the compounds of formula (I).

The metal salt complexes of the compounds of formula (I) can be obtained in a simple manner using conventional methods, for example by dissolving the metal salt in alcohol, for example in ethanol, and then adding the solution to compounds of formula (I). The metal salt complexes can be isolated in a known manner, for example by filtration, and optionally purified by recrystallization.

The compounds according to the present invention exhibit and provide a strong microbicidal activity and can thus be used to combat undesirable microorganisms, such as pathogenic fungi and bacteria, in agriculture and horticulture. The compounds are suitable for the direct controlled control of undesirable microorganisms as well as for generating resistance in plants against attack by undesirable microorganisms.

In the present invention, resistance-inducing substances are to be understood as substances which are capable of stimulating the defence system of plants so that the treated plants, when subsequently inoculated with undesirable microorganisms, develop a significant resistance to these microorganisms.

Undesirable microorganisms are to be understood in the present case as phytopathogenic fungi and bacteria. The substances according to the invention can thus be used to produce resistance in plants against attack by the harmful organisms which occur within a certain period of time after treatment. The period of time in which the resistance is established is generally 1 to 10 and preferably 1 to 7 days after treatment of the plants with the active compounds.

In general, the compounds according to the invention can be used as fungicides for controlling phytopathogenic fungi such as Plasmodiophoromycetes, Oomycetes, Chytridiomycetes, Zgomycetes, Ascomycetes, Basidiomycetes and Deuteromycetes, and also as bactericides for controlling bacteria such as Pseudomonoadaceae, Rhizobiaceae, Enterobacteriaceae, Corynebacteriaceae and Streptomycetaceae.

Some causative organisms of fungal and bacterial diseases included under the above main groups are now mentioned as non-limiting examples: Xanthomonas species, such as Xanthomonas campestris pv.oryzae; Pseudomonas species, such as Pseudomonas syringae pv.lachrymans; Erwinia species, such as Erwinia amylovora; Pythium species, such as Pythium ultimum; Phytophthora species, such as Phytophthora infestans; Pseudoperonospora species, such as Pseudoperonospora cubensis; Plasmopara species, such as B. Plasmopara viticola; Peronospora species, such as B. Peronospora pisio pv.brassicae; Erysiphe species, such as B. Erysiphe graminis; Sphaerotheca species, such as B. Sphaerotheca fuliginea, Podosphaera species, such as. B. Podosphaera leucotricha; Venturia species, such as B. Venturia inaequalis; Pyrenophora species, such as B. Pyrenophora teresor P. graminea (conidial form: Drechslera, synonym: Helminthosporium); Cochliobolus species, such as B. Cochliobolus sativus (conidial form: Drechslera, synonym: Helminthosporium); Uromyces species, such as B. Uromyces appendiculatus; Puccinia species, such as B. Puccinia recondita, Tilletia species, such as. B. Tilletia caries; Ustilago species, such as B. Ustilago nudaor, Ustilago avenae; Pellicularia species, such as B. Pellicularia sasakii; Pyricularia species, such as B. Pyricularia oryzae; Fusarium species, such as B. Fusarium culmorum; Botrytis species, such as B. Botrytis cinerea, Septoria species, such as. B. Septoria nodorum; Leptosphaeria species, such as B. Leptosphaeria nodorum; Cercospora species such as B. Cercospora canescens; Alternaria species, such as B. Alternaria brassicae; Pseudocercosporella species, such as B. Pseudocercosporella herpotrichoides.

The good tolerance of the active compounds shown by the plants at the concentrations required to combat plant diseases allows and enables the treatment of above-ground parts of the plants, vegetative reproductive stocks and seeds as well as the soil.

The active compounds can be converted into the usual formulations, such as solutions, emulsions, wettable powders, suspensions, powders, foams, pastes, granules, tablets, aerosols, natural and synthetic materials impregnated with the active compound, very fine capsules in polymeric substances as well as in coating compositions for application to seeds, and in formulations to be used with incense, such as incense cartridges, cans and coils, as well as in ULV cold and warm mist formulations.

These formulations or preparations can be produced in a known manner, for example by mixing the active compounds with extenders (extenders), ie liquid or liquefied gaseous or solid diluents or carriers, optionally using surface-active agents, ie emulsifying and/or dispersing and/or foaming agents. When using water as an extender, organic solvents can also be used, for example as auxiliary solvents.

Suitable liquid solvent diluents or carriers are mainly aromatic hydrocarbons such as xylene, toluene or Alkylnaphthalenes, chlorinated aromatic or chlorinated aliphatic hydrocarbons such as chlorobenzenes, chloroethylenes or methylene chloride, aliphatic hydrocarbons such as cyclohexane or paraffins, e.g. mineral oil fractions, alcohols such as butanol or glycol and their ethers and esters, ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone, or strongly polar solvents such as dimethylformamide and dimethyl sulfoxide, as well as water.

Liquefied gaseous diluents and carriers are liquids that are gaseous at normal temperature and pressure, e.g. aerosol propellants such as halogenated hydrocarbons as well as butane, propane, nitrogen and carbon dioxide.

Solid carriers may include ground or natural minerals such as kaolins, clays, talc, lime, quartz, attapulgite, montmorillonite or diatomaceous earth, and ground synthetic minerals such as highly dispersed silica, alumina and silicates. Solid carriers for grains may include crushed and fractionated natural stone products such as calcite, marble, pumice, sepiolite and dolomite, as well as synthetic grains of inorganic and organic flour products and grains of organic material such as sawdust, coconut shells, corn cobs and tobacco stalks.

As emulsifying and/or foaming agents, non-ionic and anionic emulsifiers such as polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, e.g. alkylaryl polyglycol ethers, alkyl sulfonates, alkyl sulfates, aryl sulfonates and albumin hydrolysis products can be used. Dispersants include, e.g., lignin sulfite waste liquid and methyl cellulose.

Adhesives such as carboxymethylcellulose and natural and synthetic polymers in the form of powders, granules or latices, such as gum arabic, polyvinyl alcohol and polyvinyl acetate, can also be used in the formulation.

It is also possible to use colorants such as inorganic pigments, e.g. iron oxide, titanium oxide and Prussian blue, and organic dyes, such as alizarin, azo or metal phthalocyanine dyes, and trace nutrients, such as salts of iron, manganese, boron, copper, cobalt, molybdenum and zinc.

The formulations generally contain 0.1 to 95 and preferably 0.5 to 90 wt.% of the active compound.

The active compounds according to the invention can be used in the formulations or in the various application forms as a mixture with other known active compounds, such as fungicides, bactericides, insecticides, acaricides, nematicides, herbicides, bird repellents, growth factors, plant nutrients and soil structure improvers.

The active compounds can be used as such in the form of their formulations or of application forms prepared therefrom by further dilution, such as in the form of ready-to-use solutions, emulsions, suspensions, powders, pastes and granules. They are applied in conventional ways, e.g. by watering, dipping, spraying, atomizing, evaporating, vaporizing, injecting, forming a slurry, brushing, dusting, sprinkling, dry, moist, wet or slurry application or by encrustation.

When treating parts of plants, the concentrations of the active compound in the application forms can vary within a considerable range. They are generally 1 to 0.0001 and preferably 0.5 to 0.001% by weight.

For the treatment of seeds, the amounts of the active compound are generally 0.001 to 50 and in particular 0.01 to 10 g per kg of seed.

For soil treatment, the concentrations of the active compound at the point of action are generally 0.00001 to 0.1 and in particular 0.0001 to 0.02 wt.%.

Preparation and use of the active compound according to the invention will now become apparent from the following examples. Synthesis Example 1

(Procedure b)

2-(3'-Amino-2'-benzylthiobenzoyl)-1-methylimidazole (7.5 g) was added to concentrated hydrochloric acid (24 mL) in water (10 mL) at 40ºC. The mixture was stirred at 40ºC for 20 min and then cooled to -5ºC. A solution of sodium nitrite (1.6 g) in water (10 mL) was added dropwise. After completion of the dropwise addition, the mixture was stirred at 0ºC for 2 h and then for a further 2 h at room temperature. The reaction mixture was Extracted twice with dichloromethane. The extract was washed with water and dried over anhydrous sodium sulfate. The organic layer was concentrated under reduced pressure and the remaining residue was purified by silica gel column chromatography (eluent: chloroform). 2-(1',2',3'-benzothiadiazol-7'-yl)carbonyl-1-methylimidazole (1.2 g) was thus obtained.

Melting point: 187 to 188.5ºC Synthesis example 2:

(Procedure a):

9.9 g of 7-chlorocarbonyl-1,2,3-benzothiadiazole was added dropwise to a solution of 4.1 g of 1-methylimidazole and 4.4 g of pyridine in 300 mL of dichloromethane with stirring and ice-cooling. After completion of the reaction, the reaction mixture was then washed with 3% aqueous hydrochloric acid (solution), 3% aqueous sodium hydroxide solution and water. The organic layer was dried over anhydrous sodium sulfate. The organic layer was then concentrated under reduced pressure and purified by silica gel column chromatography (eluent: chloroform). 2-(1',2',3'-benzothiadiazol-7'-yl)carbonyl-1-methylimidazole (1.2 g) was thus obtained.

Melting point: 187-188.5ºC Synthesis example 3

(Procedure d):

A mixture of 3-(1',2',3'-benzothiadiazol-7'-yl)carbonyl-1,2,4-triazole (1.2 g), acetonitrile (50 mL), calcium carbonate (0.7 g) and methyl iodide (0.7 g) was heated with stirring for 3 h. The reaction mixture was then evaporated under reduced pressure and the residue was purified by silica gel column chromatography (eluent: chloroform). 3-(1',2',3'-benzothiadiazol-7'-yl)carbonyl-1-methyl-1,2,4-triazole (1.3 g) was thus obtained.

Melting point: 196-198ºC Synthesis example 4

(Procedure c):

5-(1',2',3'-Benzothiadiazol-7'-yl)carbonyl-1-methoxymethyl-1,2,4-triazole (2 g) was added to concentrated hydrochloric acid (100 mL) and the mixture was heated with stirring at 80-90 °C for 30 min. The reaction mixture was then evaporated to dryness under reduced pressure and the residue was recrystallized from ethanol.

5-(1',2',3'-Benzothiadiazol-7'-yl)carbonyl-1,2,4-triazole (1.2 g) was obtained in this way.

Melting point: > 300ºC

The following Table 2 shows the compounds of formula (I) synthesized according to the above procedures. Table 2 Table 2 (continued) Table 2 (continued)

Preparation of intermediate compounds: Synthesis example 5 Starting material for the compound of Synthesis Example 1:

2-(2'-Benzylthio-3'-nitrobenzoyl)-1-methylimidazole (8.6 g) was hydrogenated in ethanol in the presence of 5% palladium-carbon (6.0 g). After completion of the reaction, the catalyst was filtered off and the solution was distilled under reduced pressure. 2-(3'-Amino-2'-benzylthiobenzoyl)-1-methylimidazole (8.0 g) was thus obtained.

Refractive index: n = 1.6513 Synthesis example 6 Starting material for the compound of synthesis example 5:

Benzyl mercaptan (4.3 g) and potassium carbonate (4.8 g) were added to a solution of 2-(2'-chloro-3'-nitrobenzoyl)-1-methylimidazole (9.2 g) in 150 mL of N,N-dimethylformamide. The reaction mixture was stirred at 80 °C for 5 h. Then, the reaction mixture was poured into ice water, and the resulting mixture was extracted twice with ethyl acetate. The combined organic layers were washed with water and then dried over anhydrous sodium sulfate. The organic layer was concentrated under reduced pressure, and the remaining residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate = 95:5 v/v). 2-(2'-benzylthio-3'-nitrobenzoyl)-1-methylimidazole (8.7 g) was thus obtained.

Refractive index: n = 1.6575 Synthesis example 7 Starting material for the compound of Synthesis Example 6

2-Chloro-3-nitrobenzoyl chloride (10.9 g) was added dropwise to a solution of triethylamine (5.0 g) and 1-methylimidazole (4.1 g) in 200 mL of dichloromethane with stirring and ice-cooling. The reaction mixture was stirred at room temperature for 8 h and then washed successively with 3% aqueous hydrochloric acid, 3% aqueous sodium hydroxide solution and water. The organic layer was concentrated under reduced pressure and the remaining residue was purified by silica gel column chromatography (eluent: chloroform/ethanol = 99:1 v/v). 2-(2'-chloro-3'-nitrobenzoyl)-1-methylimidazole (9.8 g) was thus obtained.

Melting point: 149-155.5ºC

Biological test examples Test example A Testing the effectiveness of a foliar spray against rice blast/mildew Preparation of formulations of the tested compounds

Active compound: 30 to 40 parts by weight

Carrier: Mixture of diatomaceous earth and kaolin (1 : 5), 55-65 parts by weight

Emulsifier: polyoxyethylene alkylphenyl ether, 5 parts by weight

Each of the wettable powders was prepared by pulverizing and mixing the above amounts of active compound, carrier and emulsifier. A portion of the wettable powder containing the prescribed amount of active compound is diluted with water to be subjected to the test described below.

Test procedure

Seedlings of legume rice (cultivar: Kusabue) were planted in plastic pots each with a diameter of 7 cm. The pre-prepared solution of the prescribed concentration of active compound was sprayed over the foliage of the seedlings at the 1.5 leaf stage in an amount of 50 mL per 3 pots. 10 days after the application, a suspension of artificially grown Pyricularia oryzae spores was inoculated on the seedlings by spraying and the seedlings were kept at 25ºC and 100% RH for infection. 7 days after the inoculation, the degree of infection per pot was examined and evaluated according to the following criteria evaluated. Furthermore, the comparative value (%) was calculated. Furthermore, the phytotoxicity was simultaneously investigated. The results are shown in Table 3 below. The data in Table 3 are average values of the results from 3 pots in 1 plot.

Degree of infection Percentage of injured area (%)

0 0

0.5 more than 2

1 2 to less than 5

2 5 to less than 10

3 10 to less than 20

4 20 to less than 40

5 not less than 40

Comparison value (%) = = (1-(degree of infection in the treated plot/degree of infection in the non-treated plot)) · 100

Test example B Testing the effect of a water surface application against rice blast/mildew Test procedure

Seedlings of legume rice (cultivar: Kusabue) at the 1.5-leaf stage were planted in watered plastic pots (100 cm²) at 1 seedling per pot. Seven days after planting (when the seedlings were at the 3-4-leaf stage), the solution of the prescribed concentration of the active compound prepared in a similar manner as in Test Example A was dropped onto the water surface in an amount of 10 mL per pot with a pipette. Twenty days after the chemical treatment, a suspension of artificially cultured rice mildew (mildew fungus race C) spores was inoculated onto the seedlings by spraying twice, and the seedlings were kept in the inoculation box at 25ºC and 100% RH for 12 hours for infection. Thereafter, the seedlings were transferred to a greenhouse for further handling. Ten days after inoculation, the infection degree per pot was evaluated and the comparative value (%) was calculated in a similar manner to Test Example A. Furthermore, phytotoxicity was examined at the same time. The results are shown in Table 3 below.

Test example C Testing a spray against tomato mildew Production of formulations of active compounds

Active compound: 30 to 40 parts by weight

Emulsifier: polyoxyethylene alkylphenyl ether, 5 parts by weight

Wettable powders were prepared by pulverizing and mixing the above amount of active compound, carrier and emulsifier. A portion of the wettable powder containing the prescribed amount of active compound is diluted with water to be subjected to the test described below.

Test procedure

About 5 seeds of tomato (cultivar: Kurihara) were sown in each vinyl plastic pot of 7 cm in diameter and grown in a greenhouse (at 15 to 25ºC). The solution obtained by diluting the formulation of the test compound prepared at the prescribed concentration as above was sprayed at a rate of 25 mL per 3 pots over small seedlings which had reached the 4-leaf stage. Ten days after spraying, the zoosporangia formed on lesions previously infected and diseased with Phytophthora pests were washed down with a writing brush in distilled water to prepare a suspension. The suspension was inoculated by spraying onto the treated plants, which were then kept in a greenhouse at 15 to 20ºC. Seven days after inoculation, the infection degree per pot was evaluated and the comparative value was calculated in a similar manner to Test Example A. Phytotoxicity was examined simultaneously. The results are shown in Table 3. The data are averages of the results from 3 pots in 1 plot.

Test example D Testing a spray against powdery barley mildew Test procedure

About 10 seedlings of barley (cultivar: Haruna 2jyo) were sown in each vinyl plastic pot of 7 cm diameter and grown in a greenhouse at 15 to 25ºC. The solution obtained by diluting the formulation of the test compound prepared in a similar manner to Test Example C was sprayed at a rate of 25 mL per 3 pots over small seedlings that had reached the 2-leaf stage. Five days after spraying, the condiospores formed on lesions that were previously infected with Eryiphe graminis and were diseased accordingly were sprinkled over the treated barley leaves for inoculation. The plants were kept in a greenhouse at 15 to 20ºC. 7 Days after inoculation, the infection level per pot was evaluated and the comparative value was calculated in a similar manner to Test Example A. Phytotoxicity was examined simultaneously. The results are also shown in Table 3. The data are averages of the results from 3 pots in 1 plot. Table 3

In the table:

++++ Comparison value, 95% or higher

+++ Comparison value, 85% or higher

++ Comparison value, 70% or higher

+ Comparison value, 50% or higher

No phytotoxicity was observed in all tests.

Claims

1. 1,2,3-Benzothiadiazole derivatives of the formula:

where Het is:

and what

R¹ Hydrogen, C1-4 alkyl, C1-4 haloalkyl, phenyl-C1-4 alkyl, cyano-C1-4 alkyl, C1-2 Alkoxy-C1-4 alkyl, C1-2 alkylthio-C1-4 alkyl, C1-2 alkoxycarbonyl-C1-4 4 alkyl, C2-4 alkenyl, phenyl, halogen-substituted phenyl or C1-4 alkyl-substituted phenyl and

R² and R³, independently of each other, are hydrogen or C₁₋₄-alkyl,

as well as acid addition salts and metal salt complexes thereof.

2. 1,2,3-benzothiadiazole derivatives of formula (I) according to claim 1, in which Het is:

wherein

R¹ hydrogen, methyl, ethyl, propyl, isopropyl, butyl, cyanomethyl, 2-cyanoethyl, 1-cyanoethyl, 3-cyanopropyl, methoximethyl, ethoxymethyl, methylthiomethyl, Methoxycarbonylethyl, ethoxycarbonylmethyl, ethoxycarbonylethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, benzyl, phenyl, chlorophenyl, methylphenyl, vinyl, ally, or but-3-en-1-yl and

R² and R³, independently of one another, are hydrogen, methyl, ethyl, propyl, isopropyl or t-butyl.

3. Process for the preparation of 1,2,3-benzothiadiazole derivatives of the formula (I) according to claim 1 and of acid addition salts and metal salt complexes thereof, characterized in that

a) 1,2,3-benzothiadiazolylcarbonyl halides of the formula:

wherein

where Hal is chlorine or bromine,

with heterocycles of the formula:

Het¹-H (III),

where Het¹ represents:

in which

R&sup4; C1-4 alkyl, C1-4 haloalkyl, phenyl-C1-4 alkyl, cyano-C1-4 alkyl, C1-2 alkoxy-C1 ;-4 alkyl, C1-2 alkylthio-C1-4 alkyl, C1-2 alkoxycarbonyl-C1-4 alkyl, C2- 4 -alkenyl, phenyl, halogen-substituted phenyl or C 1-4 alkyl-substituted phenyl,

or in which

Het¹ represents:

wherein

R² and R³ have the meanings given above,

in the presence of an inert diluent and, if necessary, in the presence of a binding agent for acids,

or that one

b) Phenyl derivatives of the formula:

where Het¹ has the meanings given above and

R⁵ is hydrogen, methyl, isopropyl, benzyl or acetyl,

reacting with nitrous acid or a salt thereof in the presence of an inert diluent under acidic conditions,

or that one

c) 1,2,3-benzothiadiazole derivatives of the formula:

wherein

Het² is

with an acid and, if appropriate, in the presence of an inert diluent,

or that one

d) 1,2,3-benzothiadiazole derivatives of the formula:

where Het³ is:

with halogen compounds of the formula:

R6-Hal¹ (V)

in which

R&sup6; C1-4 alkyl, C1-4 haloalkyl, phenyl-C1-4 alkyl, cyano-C1-4 alkyl, C1-2 alkoxy-C1 ;-4 alkyl, C1-2 alkylthio-C1-4 alkyl, C1-2 alkoxycarbonyl-C1-4 alkyl or C2-4 alkyl. -alkenyl and

Hal¹ are chlorine, bromine or iodine,

4. Microbicidal compositions, characterized in that they contain at least one 1,2,3-benzothiadiazole derivative of the formula (I) according to claim 1 or an acid addition salt or a metal salt complex of a 1,2,3-benzothiadiazole derivative of the formula (I).

5. Method for controlling undesirable microorganisms, characterized in that 1,2,3-benzothiadiazole derivatives of the formula (I) according to claim 1 or acid addition salts or metal salt complexes thereof are applied to the microorganisms and/or their habitat.

6. Use of 1,2,3-benzothiadiazole derivatives of the formula (I) according to claim 1 or of acid addition salts or metal salt complexes thereof for combating undesirable microorganisms.

7. Process for the preparation of microbicidal compositions, characterized in that 1,2,3-benzothiadiazole derivatives of the formula (I) according to claim 1 or acid addition salts or metal salt complexes thereof are mixed with extenders and/or surfactants.

8. Phenyl derivatives of the formula:

where Het¹ represents

wherein

or in which

Het¹ represents:

where R² and R³ are independently hydrogen or C₁₋₄-alkyl and

R⁵ is hydrogen, methyl, isopropyl, benzyl or acetyl.

9. Process for the preparation of the phenyl derivatives of the formula (IV) according to claim 8, characterized in that

e) Nitrophenyl derivatives of the formula:

where Het¹ and R⁵ have the above meanings,

with reducing agents in the presence of an inert diluent and, if appropriate, in the presence of a catalyst.

10. Nitrophenyl derivatives of the formula:

in which

Het¹ represents:

wherein

R4; C1-4 alkyl, C1-4 haloalkyl, phenyl-C1-4 alkyl, cyano-C1-4 alkyl, C1-2 alkoxy-C1-4 alkyl, submin2 alkylthio-C1-4 alkyl, C1-2 alkoxyicarbonyl-C1-4 alkyl, C2-4 alkenyl, phenyl, halogen-substituted phenyl or C1-4 alkyl substituent ated phenyl is,

or in which Het¹ represents:

wherein R² and R³, independently of one another, are hydrogen or C₁₋₄alkyl and

R⁵ is hydrogen, methyl, isopropyl, benzyl or acetyl.

11. Process for the preparation of the nitrophenyl derivatives of the formula (VI) according to claim 10, characterized in that

f) Chloronitrophenyl derivatives of the formula:

where Het¹ has the above meanings,

with sulphur compounds of the formula:

HS-R5 (VIII),

wherein R5 has the above meanings,

in the presence of an inert diluent and, if appropriate, in the presence of a binding agent for acids.

12. Chloronitrophenyl derivatives of the formula:

in which Het¹ represents:

wherein

or in which Het¹ represents:

wherein R² and R³ are independently hydrogen or C₁₋₄alkyl .

13. Process for the preparation of the chloronitrophenyl derivatives of the formula (VII) according to claim 12, characterized in that

g) 2-chloro-3-nitrobenzoyl chloride of the formula:

with a heterocycle of the formula:

Het¹-H (III),

where Het¹ has the above meanings,

in the presence of an inert diluent and, if necessary, in the presence of a binding agent for acids.